Acid-base balance and its disorders

Figure is found on http://www.mfi.ku.dk/ppaulev/chapter17/Chapter%2017.htm

Pavla Balínová

Definitions• Acid (HA) is defined as a compound that can

release a proton (H+)• Acidosis (acidaemia) is defined as a disorder

with accumulation of acids in the extended ECV. The pH in the arterial blood is < 7.35

• Base (B-) can bind H+

• Alkalosis (alkalaemia) is defined as a condition with accumulation of bases in the extended ECV. The pH of the arterial blood is › 7.45 

• Buffer is a mixture of compounds which have the ability to absorb small amounts of H+ or OH- with very little change of pH.

pH = pK + log cs / cA

Proton concentration and pH

Normally, the [H+] of arterial blood of humans is maintained by the lungs, kidneys and liver within the range of 40 5 nM, corresponding to a pH of 7.35 - 7.45. pH = - log (40 x 10-9 mol/L ) = 7.4

A pH of 6.8 - 6.9 is not sustainable for long, and the patient is dying in a state of coma.

Figure is found on http://www.mfi.ku.dk/ppaulev/chapter17/Chapter%2017.htm

Production of acids● CO2 is a potential acid as H2CO3, and because the lungs eliminate it, it is called a volatile acid. Production of CO2 is up to 24 mol daily.

● Non-volatile acids:a) organic acids are continually produced as a by-product of metabolism:- anaerobic glycolysis in muscles and ery → lactic acid → lactate + H+

- ketogenesis → acetoacetic acid → acetoacetate + H+ → β-hydroxybutyric acid → β-hydroxybutyrate + H+ - lipolysis → TAG → 3 FA + glycerol + 3 H+

- urea synthesis in liver: CO2 + 2 NH4 → urea + H2O + 2 H+

Under normal conditions, these acids are completely metabolized to CO2 and H2O. They have no effect on proton balance.

b) inorganic acids: excretion by kidneysH2SO4 → HSO4

- + H+

H3PO4 → HPO42- + H+

Note: H+ are also released from acids in the diete. g. citric acid, ascorbic acid

Consumption of acids (protons)

• gluconeogenesis: 2 lactate + 2 H+ → Glc• oxidation of neutral AA and Glu and Asp

The body maintains ECF physiologic pH by buffers

• Bicarbonate buffer HCO3- / CO2 (53%)

• Hemoglobin (Hb) – in ery (35%)• Plasma proteins (mainly albumin) (7%)• Phosphate buffer HPO4

2- / H2PO4- (3%)

NH3/NH4+ and HPO4

2-/H2PO4- are the most important

urinary buffer systems.About 30 mmol of NH4

+ is excreted in the daily urine, but the excretion is controlled during acid-base disorders.

HCO3-/CO2

system is an effective open buffer system

HCO3- and CO2 are present in ratio of about 20 : 1.

CO2 is dissolved in the plasma and it is constantly exchanging with CO2 in the gas phase of the alveoli of the lungs.

Henderson-Hasselbach equation for HCO3-/CO2 system:

pH = pK + log [HCO3-] / [H2CO3]

pH = pK + log [HCO3-] / pCO2 x α

pH = 6.1 + log 24 / 40 x 0.03 (pCO2 = 40 mmHg →factor α = 0.03)

pH = 6.1 + log 20pH = 6.1 + 1.3 = 7.4

Conversion: 1 kPa = 7.5 mmHg 1 mmHg = 133.22 Pa

CO2 (pCO2) elimination is controlled by lungs (respiratory system). It takes 1 – 3 min to respond to changes in pH and effect changes in the pH.↑ ventilation → ↓ pCO2 → alkalinization

↓ ventilation → ↑ pCO2 → acidification

HCO3- elimination is controlled by kidneys. It takes several

hours to days for urinary system to compensate for changes in pH.

Liver: CO2 + 2 NH4 → urea + 2 H+ + H2O

NH4+ + Glu → Gln + H2O

Laboratory analysis of ABB state

• Determination of pH, HCO3-, pCO2, pO2 and BE

• Determination of concentration of cations (Na+, K+, Ca2+, Mg2+), concentration of anions (Cl-, lactate) and metabolites (urea, creatinine, ketone bodies)

Normal values of:• HCO3

- = 22 – 26 mmol/L• BE = from – 2.5 to + 2.5 mmol/L

BE (base excess) is defined as the amount of acid that would be added to blood to titrate it to pH 7.4 at pCO2 = 40 mmHg. positive value = base excess negative value = base deficit (BD)

Astrup determination is based on measurement of pH, pCO2, pO2 in blood

It is measured by special electrodes in automatic apparatus. An arterial blood sample is used.

Normal values of arterial blood: • pH = 7.35 – 7.45

• pCO2 = 4.8 – 5.8 kPa = 36 – 43.5 mmHg

• pO2 = 9.8 – 14.2 kPa = 73.5 – 106.5 mmHg

These values are measured directly. Concentration of HCO3

- and BE are calculated from measured values by software in automatic apparatus.

Astrup apparatus

• Glass electrode – pH• Membrane electrode –

pCO2

• Clark´s oxygen electrode – pO2

Anion gap (AG)

AG represents the plasma anions which are not routinely measured (albumin, phosphates, sulphates, organic anions).AG is calculated as follows:AG = (Na+ + K+) – (HCO3

- + Cl-)

The sum of the concentrations of Na+ and K+ is greater than the sum of concentrations of HCO3

- and Cl-. Difference is called as a anion gap.Normal values of AG: 16 – 20 mmol/L

AG is calculated in case of metabolic acidosis.

ABB disorders

ACIDOSIS

respiratory metabolic

ALKALOSIS

respiratory metabolic

Compensation of ABB disorders

• Metabolic disorder is compensated by respiration and

conversely

Correction of ABB disorders• Metabolic disorder is corrected by metabolic

processes

Respiratory acidosis (RAc)

RAc is caused by hypoventilation (or breathing of CO2 containing air). Hypoventilation is associated with an impaired ability to eliminate CO2, whereby pCO2 increases and the accumulated CO2 reduces the

arterial pH.

Causes: airway obstruction, neuromuscular disorders, disorders of CNS, opiate poisoning

Compensation: ↑ reabsorption of HCO3- is performed

by kidneys (proximal tubule)

Respiratory alkalosis (RAl)

The hyperventilation is disproportionately high compared to the CO2 production, whereby the pCO2

falls and the pH increases

Causes: CNS injury, salicylate poisoning, fever, …Other typical cases are the anxious patient during an attack of asthma or the hysterical hyperventilation in neurotic patients.

Compensation: ↑ renal excretion of HCO3

- → plasma pH decreases toward normal pH

Metabolic acidosis (MAc)

● MAc is caused by accumulation of acids in ECF. ● negative BE

Causes: • hypoxia is a lack of O2 in tissues → anaerobic

glycolysis produces lactic acid → lactate acidosis• overproduction of ketone bodies → ketoacidosis

(DM, starvation)• ingestion of methanol or ethylene glycol• diarrhoea

Compensation:1st step: buffering of excess of H+ by HCO3

-

2nd step: respiratory compensation by hyperventilation3rd step: renal correction → ↑ excretion of H+ in urine

Metabolic alkalosis (MAl)

MAl is caused by a primary accumulation of bases in ECF. Both the [bicarbonate] and the [non-carbonic buffer base] are increased, so the BE is increased. Causes:

• ingestion of alkaline drugs (e. g. NaHCO3)

• prolonged vomiting → loss of H+

Compensation:1st step: buffering of excess of HCO3

-

2nd step: respiratory compensation by hypoventilation → ↑ pCO2 in alveoli and arterial blood

3rd step: renal correction: ↑ excretion of HCO3- in urine

Case report 1A young man was injured in the chest from a car accident. Instrument ventilation was started.

plasma measured valuesHCO3

- 25 mmol/L

AstruppH 7.24pCO2 60 mmHg = 8 kPapO2 60 mmHg = 8 kPa

Type of ABB disorder??

Solution of case report 1

Respiratory acidosis without compensation. Hypoventilation is a cause of ↑ pCO2 in arterial blood.

Case report 2

A 45 year old man was admitted with a history of persistent vomiting. He had a long history of dyspepsia. Examination revealed dehydration and shallow respiration.

plasma measured values K+ 2.8 mmol/LHCO3

- 45 mmol/Lurea 34 mmol/LAstruppH 7.56pCO2 54 mmHg = 7.2 kPa

Type of ABB disorder??

Solution of case report 2

Metabolic alkalosis is a result of persistent vomiting loss of H+ and dehydration. Small amount of urine (lower diuresis) is a cause of higher concentration of urea in blood.

Respiratory compensation was started (hypoventilation) → ↑ pCO2.

Lower K+ concentration indicates alkaleamia.

Case report 3A 23 year old mechanic was admitted to hospital 12 hours after drinking antifreeze.He was given 400 mmol of HCO3

- with a little effect. Dialysis was started but he went to shock and died 12 hours after admission.

plasma admission dialysis 4 hours

Na+ 137 mmol/L 145 mmol/LK+ 5.4 mmol/L 4.9 mmol/LCl- 95 mmol/L 87 mmol/LHCO3

- 4 mmol/L 5 mmol/LGlc 2.5 mmol/L AstruppH 6.95 7.05 7.29pCO2 15 mmHg 16 mmHg 25 mmHg = 3.33 kPa

Type of ABB disorder??

Solution of case report 3

Metabolic acidosis is due to antifreeze poisoning. Antifreeze contains ethylene glycol which is oxidized to oxalic acid in body.

After 12 hours, the respiratory compensation was started → hyperventilation → ↓ pCO2.

Cause of his death is a renal failure due to oxalates in kidneys.

Case report 4

A young woman was admitted 8 hours after taking an overdose of aspirin.

plasma measured valuesHCO3

- 12 mmol/L

AstruppH 7.53pCO2 15 mmHg = 2 kPa

Type of ABB disorder??

Solution of case report 4

Respiratory alkalosis is due to overdose of aspirin.

pCO2 is decreased because patient has a hyperventilation.

Renal compensation was started → excretion of HCO3-.